Raymond W. H. Yung

Facemasks and Hand Hygiene to Prevent Influenza Transmission in Households: A Cluster Randomized Trial

Context Hand hygiene and use of facemasks are key elements of influenza pandemic preparedness plans, but their effects on preventing transmission of infection have not been demonstrated. Contribution In this cluster randomized trial, hand washing and facemasks seemed to prevent influenza transmission when healthy family members started using these measures within 36 hours of symptom onset in an infected family member. Caution Adherence to the interventions was low. Implication Hand hygiene and facemasks seem to reduce influenza virus transmission when implemented early after symptom onset. The Editors Interpandemic human influenza virus infects millions of people every year. Some infections are mild, but othersespecially in young or elderly personscan result in more severe illness requiring hospitalization. Influenza is associated with hundreds of thousands of deaths worldwide annually (1, 2). The 2009 swine-origin influenza A (H1N1) pandemic highlighted the importance of identifying public health measures to mitigate influenza virus transmission. Many countries would use nonpharmaceutical interventions, including facemasks, improved hand hygiene, cough etiquette, isolation of sick and quarantine of exposed individuals, social distancing measures, and travel restrictions, as their primary means to mitigate an influenza pandemic, particularly at its beginning (310). However, data are scarce on the effectiveness of simple personal protective measures, such as facemasks and hand hygiene, against pandemic or interpandemic influenza and on the modes of influenza virus transmission among people (5, 11). After a pilot study in 2007 (12), we conducted a prospective cluster randomized trial to test whether improved hand hygiene or surgical facemasks reduce the transmission of interpandemic influenza in households. We used a cluster design with randomization to interventions at the household level to avoid difficulties in blinding and potential contamination of interventions. Methods Design From 45 outpatient clinics in the private and public sectors across Hong Kong, we enrolled persons who reported at least 2 symptoms of acute respiratory illness (temperature37.8C, cough, headache, sore throat, or myalgia); had symptom onset within 48 hours; and lived in a household with at least 2 other people, none of whom had reported acute respiratory illness in the preceding 14 days. After participants gave informed consent, they provided nasal and throat swab specimens, which were combined and tested with the QuickVue Influenza A+B rapid diagnostic test (Quidel, San Diego, California). Participants with a positive rapid test result and their household contacts were randomly assigned to 1 of 3 study groups: control (lifestyle measures), control plus enhanced hand hygiene only, and control plus facemasks and enhanced hand hygiene. Table 1 provides detailed descriptions of the interventions. Data on clinical signs and symptoms were collected for all participants. An additional nasal and throat swab specimen was collected for laboratory confirmation of influenza virus infection by reverse-transcription polymerase chain reaction (RT-PCR). Table 1. Study Interventions Randomization lists were prepared by a biostatistician. The households of eligible study index patients were allocated to 3 groups in a 1:1:1 ratio under a block randomization structure with randomly permuted block sizes of 18, 24, and 30 by using a random-number generator (R software, R Development Core Team, Vienna, Austria). Interventions were assigned to households by the study manager on the basis of the randomization sequence. The allocation to specific intervention groups was concealed to recruiting physicians and clinics throughout the study. Participants and people who administered the interventions were not blinded to the interventions, but participants were not informed of the specific nature of the interventions applied to other participating households. After randomization, a home visit was scheduled within 2 days (ideally within 12 hours) to implement the intervention and to collect informed consent, baseline demographic data, and nasal and throat swab specimens from all household members 2 years of age or older. During the home visit, index patients and household contacts were instructed in the proper use of a tympanic thermometer. During the 6 days after the initial home visit, all household contacts were asked to keep daily symptom diaries. Further home visits were scheduled around 3 and 6 days after the baseline household visit to monitor adherence to interventions and to collect further nasal and throat swab specimens from all household members regardless of illness. During the final home visit, study nurses collected and reviewed symptom diaries, and they evaluated adherence to interventions by interview and by counting the number of surgical masks remaining and weighing the amount of soap and alcohol left in bottles and dispensers. Households were reimbursed for their participation with a supermarket coupon worth approximately U.S.

Development of a standard treatment protocol for severe acute respiratory syndrome

25. All participants 18 years or older gave written informed consent. Proxy written consent from parents or legal guardians was obtained for persons 17 years or younger, with additional written assent from those 8 to 17 years of age. The study protocol was approved by the institutional review board of The University of Hong Kong and the Hospital Authority Hong Kong West Cluster. Outcome Measures The primary outcome measure was the secondary attack ratio at the individual level: the proportion of household contacts infected with influenza virus. We evaluated the secondary attack ratio by using a laboratory definition (a household contact with a nasal and throat swab specimen positive for influenza by RT-PCR) as the primary analysis and 2 clinical definitions of influenza based on self-reported data from the symptom diaries as secondary analyses (12). The first definition of clinical influenza was at least 2 of the following signs and symptoms: temperature 37.8C or greater, cough, headache, sore throat, and myalgia (13); the second was temperature 37.8C or greater plus cough or sore throat (14). An additional secondary outcome measure was the secondary attack ratio at the household (cluster) level: the proportion of households with 1 or more secondary case. Laboratory Methods Specimens collected from index patients at recruitment were stored in a refrigerator at 2 to 8C. Specimens collected during home visits were stored in an ice chest with at least 2 ice packs immediately after collection. Before the end of the day of a home visit, study nurses obtained samples to the nearest collection point for storage in a refrigerator at 2 to 8C. Samples stored at 2 to 8C in ice chests were delivered to the central testing laboratory at Queen Mary Hospital by courier. Samples were eluted and cryopreserved at 70C immediately after receipt. All specimens were tested by RT-PCR for influenza A and B viruses using standard methods (1517). The Appendix provides additional details of the laboratory procedures that we used. Statistical Analysis On the basis of data collected in our pilot study (12) and other studies with similar design (18, 19), we assumed that 10% to 15% of household contacts in the control group would develop RT-PCRconfirmed influenza, with an average household size of 3.8 and an intracluster correlation coefficient of 0.29. Specifying 80% power and a significance level of 5%, we aimed to follow 300 households in each intervention group to allow us to detect differences in secondary attack ratios of 35% to 45%, depending on the actual secondary attack ratios in the control group (15% or 10%, respectively). Recruiting 100 or 200 households to each group would allow 80% power to detect 55% to 70% and 45% to 55% differences in secondary attack ratios, assuming a secondary attack ratio of 10% to 15% in the control group. To evaluate and compare secondary attack ratios by intervention group, we estimated 95% CIs by using a cluster bootstrap technique with 1000 resamples (20) and chi-square tests and multivariable logistic regression models adjusting for potential within-household correlation (21, 22). We estimated the intracluster correlation coefficient from the mean squared errors in the secondary attack ratio between and within households (21). For the multivariable logistic regression models, we used forced-entry methods to include plausible confounders, including the intervention allocated, the age and sex of the household contacts and their corresponding index patients, vaccination status of the household contacts, and antiviral use in corresponding index patients, whereas missing data on the exact age of 14 household contacts were imputed by comparison with their relationship with the index patient or occupation. Participants were analyzed in the group to which they were randomly assigned, regardless of adherence to the intervention or use of hand washing or facemasks in groups not assigned that intervention. Our protocol specified that households with more than 1 member with RT-PCRconfirmed influenza virus infection at baseline (coindex patients) or index patients in whom influenza virus infection could not be confirmed by RT-PCR would be excluded from analyses. We excluded from analyses participants who dropped out before receiving the intervention and the few participants who dropped out after the intervention but before data on the primary outcome measure were collected (23). In sensitivity analyses, we analyzed all households in which the intervention was applied, using multiple imputation for unobserved outcomes (24) and including an additional explanatory variable for households with more than 1 index patient. Statistical analyses were conducted in R, version 2.7.1 (R Development Core Team). Role of the Funding Source The study was funded by the Centers for Disease Control and Prevention; the Research Fund for the

Clinical and Molecular Epidemiological Features of Coronavirus HKU1–Associated Community-Acquired Pneumonia

Summary A series of 31 patients with probable SARS, diagnosed from WHO criteria, were treated according to a treatment protocol consisting of antibacterials and a combination of ribavirin and methylprednisolone. Through experience with the first 11 patients, we were able to finalise standard dose regimens, including pulsed methylprednisolone. One patient recovered on antibacterial treatment alone, 17 showed rapid and sustained responses, and 13 achieved improvement with step-up or pulsed methylprednisolone. Four patients required short periods of non-invasive ventilation. No patient required intubation or mechanical ventilation. There was no mortality or treatment morbidity in this series.

Mannose-Binding Lectin in Severe Acute Respiratory Syndrome Coronavirus Infection

Abstract BackgroundRecently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1–associated pneumonia are unknown MethodsProspectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1–associated pneumonia were analyzed. The pol spike (S), and nucleocapsid (N) genes were also sequenced ResultsNPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol S, and N genes revealed 2 genotypes of CoV-HKU1 ConclusionsCoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses

Effectiveness of Noninvasive Positive Pressure Ventilation in the Treatment of Acute Respiratory Failure in Severe Acute Respiratory Syndrome

Abstract Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS

Community-associated methicillin-resistant and methicillin-sensitive Staphylococcus aureus: skin and soft tissue infections in Hong Kong

Objectives: To study the effectiveness of noninvasive positive pressure ventilation (NIPPV) in the treatment of acute respiratory failure (ARF) in severe acute respiratory syndrome (SARS), and the associated infection risk. Methods: All patients with the diagnosis of probable SARS admitted to a regional hospital in Hong Kong from March 9 to April 28, 2003, and who had SARS-related respiratory distress complications were recruited for NIPPV usage. The health status of all health-care workers working in the NIPPV wards was closely monitored, and consent was obtained to check serum for coronavirus serology. Patient outcomes and the risk of SARS transmission to health-care workers were assessed. Results: NIPPV was applied to 20 patients (11 male patients) with ARF secondary to SARS. Mean age was 51.4 years, and mean acute physiology and chronic health evaluation II score was 5.35. Coronavirus serology was positive in 95% (19 of 20 patients). NIPPV was started 9.6 days (mean) from symptom onset, and mean duration of NIPPV usage was 84.3 h. Endotracheal intubation was avoided in 14 patients (70%), in whom the length of ICU stay was shorter (3.1 days vs 21.3 days, p < 0.001) and the chest radiography score within 24 h of NIPPV was lower (15.1 vs 22.5, p = 0.005) compared to intubated patients. Intubation avoidance was predicted by a marked reduction in respiratory rate (9.2 breaths/min) and supplemental oxygen requirement (3.1 L/min) within 24 h of NIPPV. Complications were few and reversible. There were no infections among the 105 health-care workers caring for the patients receiving NIPPV. Conclusions: NIPPV was effective in the treatment of ARF in the patients with SARS studied, and its use was safe for health-care workers.

Human Parainfluenza Virus 4 Outbreak and the Role of Diagnostic Tests

This prospective study assessed the epidemiology of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among patients with purulent skin and soft tissue infections (SSTIs) in Hong Kong. Among 298 patients with SSTIs, 10.4% (13/125) of all S. aureus isolates and 5% (12/241) of all abscesses were attributed to pvl-positive CA-MRSA. Overall, 77% and 69.9% of CA-MRSA and methicillin-sensitive S. aureus (MSSA) were susceptible to erythromycin, 77% and 74.8% to clindamycin, 100% and 97.1% to minocycline, and 100% and 98.1% to rifampin, respectively. Filipino ethnicity was the only clinical and epidemiologic factor significantly associated with CA-MRSA infection (odds ratio, 14.8; 95% confidence interval, 3.3-70.0; P < 0.001). Pulsed-field gel electrophoresis analysis showed that 6 CA-MRSA isolates belonged to the ST30-HKU100 clone, 5 belonged to the ST59-HKU200 clone, and 1 was singleton. Features of HKU100 isolates include SCCmec type IV, agr3, spa t019, and pan-susceptibility to non-beta-lactam antibiotics. In contrast, HKU200 isolates are characterized by having SCCmec type IV or V, agr4, spa t437, and variable non-beta-lactam susceptibility profiles. The major CA-MRSA spa types were shared by a minority of the MSSA.

Fluoroquinolone and Other Antimicrobial Resistance in Invasive Pneumococci, Hong Kong, 1995–2001

ABSTRACT Owing to the difficulties in isolating the virus and the lack of routine surveillance, the clinical significance of human parainfluenza virus 4 (HPIV-4) is less well defined than that of the other human parainfluenza viruses. We describe the first outbreak of HPIV-4 infection in a developmental disabilities unit, involving 38 institutionalized children and three staff members, during a 3-week period in autumn 2004. Most subjects had upper respiratory tract infections (URTI), while lower respiratory tract infections (LRTI) occurred in three children (7%), one complicated by respiratory failure requiring ventilation support. All patients recovered. Nasopharyngeal aspirates tested for HPIV-4 were positive by reverse transcriptase PCR (RT-PCR) in all 41 cases (100%), by direct immunofluorescence in 29 of 39 tested cases (74%), and by cell cultures in 6 of 37 cases (16%), and serum was positive for antibodies against HPIV-4 in all 35 cases (100%) with serum samples available. In addition, RT-PCR detected HPIV-4 in four children (three LRTI and one URTI) out of 115 patients with community-acquired respiratory tract infection. Molecular analysis of the 1,198-bp phosphoprotein sequences showed that HPIV-4 isolates among the cases were genetically similar, whereas the community controls were more genetically distant, supporting nosocomial transmission of a single HPIV-4 genotype during the outbreak. Moreover, the HPIV-4 causing the outbreak is more closely related to HPIV-4A than HPIV-4B. HPIV-4 may be an important cause of more severe respiratory illness in children. The present RT-PCR assay is a sensitive, specific, and rapid method for the diagnosing HPIV-4 infection. To better define the epidemiology and clinical spectrum of disease of HPIV-4 infections, HPIV-4 should be included in the routine panels of respiratory virus detection on respiratory specimens.

Screening for family members of patients with nasopharyngeal carcinoma

Fluoroquinolone resistance among invasive pneumococci in Hong Kong was high and a result of clonal expansion and spread.

Contemporary Methicillin-Resistant Staphylococcus aureus Clones in Hong Kong

Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. Familial aggregation is evident, hence screening for early detection is offered by oncology centers in Hong Kong to first‐degree relatives of patients with NPC. During the period 1994–2001, 929 family members were screened in our center. The screenees were advised to attend an annual examination that includes serological test against Epstein Barr Virus (EBV), physical examination to exclude cervical lymphadenopathy and cranial nerve palsy, and endoscopic examination of the nasopharyngeal region. Two different methods were used for the serology test: indirect immuno‐fluorescent (IF) test for IgA against viral capsid antigen; and starting in 1997 enzyme‐linked immunosorbent assay (ELIZA) against nuclear antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were diagnosed, giving a detection rate of 5/1,155 (433/100,000) person‐year for male and 7/1,404 (499/100,000) person‐year for female participants observed. The corresponding average annual incidence in Hong Kong during this period was 24.1 and 9.6 per 100,000, respectively. Forty‐one percent of these detected cases had Stage I disease, whereas only 2% of patients referred to the department for primary treatment presented with such early disease. Six cases were detected at first visit, and all were EBV‐positive. Another 78 screenees with positive serology at first visit were followed up for 204 person years, and thus far NPC was detected in 3 after an interval of 6–32 months. Of the 845 initially EBV‐negative screenees followed up for 2,337 person‐years, NPC was detected in 3 after an interval of 12–45 months. One showed sero‐conversion at the time of diagnosis. We conclude that family members of known patients do show a substantially higher risk of developing NPC, and regular screening by current method improves the chance of early detection.